Acyl iodides in organic synthesis: XI. Unusual N-C bond cleavage in tertiary amines

Article abstract of DOI:10.1134/S1070428008040015

Acyl iodides reacted with excess primary and secondary amines in a way similar to acyl chlorides, yielding the corresponding carboxylic acid amide and initial amine hydroiodide. Reactions of tertiary amines with acyl iodides were accompanied by cleavage of the N-C bond with formation of the corresponding N,N-di(hydrocarbyl)carboxamide and alkyl iodide. In the presence of excess tertiary amine the latter was converted into quaternary tetra(hydrocarbyl) ammonium iodide.

Full text of DOI:10.1134/S1070428008040015

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2008, Vol. 44, No. 4, pp. 481–484. © Pleiades Publishing, Ltd., 2008.
Original Russian Text © M.G. Voronkov, I.P. Tsyrendorzhieva, V.I. Rakhlin, 2008, published in Zhurnal Organicheskoi Khimii, 2008, Vol. 44, No. 4,
pp. 487–489.
Acyl Iodides in Organic Synthesis: XI.* Unusual N–C Bond
Cleavage in Tertiary Amines
M. G. Voronkov, I. P. Tsyrendorzhieva, and V. I. Rakhlin
Favorskii Irkutsk Institute of Chemistry, Siberian Division, Russian Academy of Sciences,
ul. Favorskogo 1, Irkutsk, 664033 Russia
e-mail: vir@irioch.irk.ru
Received May 10, 2007
Abstract—Acyl iodides reacted with excess primary and secondary amines in a way similar to acyl chlorides,
yielding the corresponding carboxylic acid amide and initial amine hydroiodide. Reactions of tertiary amines
with acyl iodides were accompanied by cleavage of the N−C bond with formation of the corresponding N,N-di-
(hydrocarbyl)carboxamide and alkyl iodide. In the presence of excess tertiary amine the latter was converted
into quaternary tetra(hydrocarbyl)ammonium iodide.
DOI: 10.1134/S1070428008040015
It is known [2] that acyl chlorides react with pri-
mary and secondary amines in the presence of hydro-
gen chloride acceptor (inorganic or organic base or
excess initial amine) to give the corresponding carbox-
amides. While studying analogous reactions of acetyl
and benzoyl iodides with primary and secondary
amines, such as aniline, N-ethylaniline, etc., we have
found that they follow the same pattern: the products
are the corresponding amides, but the reactions are
considerably more facile.
iodide (Scheme 1). Cleavage of the N–C bond in ter-
tiary amines by the action of acyl iodides is strongly
facilitated if one of the substituents on the nitrogen
atom is a benzyl, allyl, or alkyl group. No N−Carom
bond cleavage was observed under the given condi-
tions. In the presence of excess tertiary amine, alkyl or
allyl iodide formed in the first step reacts further with
the other amine molecule to give the corresponding
quaternary tetra(hydrocarbyl)ammonium iodide.
Scheme 1.
Acyl chlorides are known [2] to react with tertiary
amines to produce either the corresponding quaternary
ammonium chlorides or ketenes (as a result of dehy-
drochlorination of the initial acyl chloride). Never-
theless, as noted in [3], prolonged heating of benzoyl
chloride with N,N-dimethyl- or N,N-diethylaniline at
190–200°C resulted in cleavage of one N–CAlk bond
with formation of N-alkyl-N-phenylbenzamide. Like-
wise, elimination of one methyl group from the initial
amine was observed in the reactions of benzoyl chlo-
ride with N,N-dimethylnaphthalen-1- and -2-amines
under severe conditions (170–190°C).
O
O
R3
N
R3
R1
N
+
+
R2I
R1
I
R2
R4
R4
R1 = Me, Ph; R2 = R3 = R4 = Et, Bu, CH2=CHCH2; R2 =
PhCH2, R3 = R4 = Me; R2 = R3 = Et, R4 = Ph.
In all cases, benzoyl iodide was more reactive than
acetyl iodide toward tertiary amines. For example, we
succeeded in obtaining N,N-dibutyl- and N,N-diallyl-
benzamides in 85 and 62% yield, respectively. In the
reactions with acetyl iodide, the yields of N,N-di(hy-
drocarbyl)acetamides were much lower (16–37%), pre-
sumably as a result of concurrent dehydroiodination of
acetyl iodide with formation of ketene.
We have found that acyl iodides react with tertiary
aliphatic and arylaliphatic amines even at room tem-
perature and that the reaction is accompanied by
cleavage of the N−C bond with formation of the cor-
responding N,N-di(hydrocarbyl)carboxamide and alkyl
The selectivity and ease of N−C bond cleavage in
the reactions of benzoyl iodide with tertiary amines
prompted us to optimize the conditions for reactions of
tertiary amines with acyl iodides having no hydrogen
* For communication X, see [1].
481

VORONKOV et al.
482
atom in the α-position, i.e., those incapable of under-
going dehydroiodination and generating ketene. In
some cases, specifically when elimination of hydrogen
iodide and its binding by appropriate HI acceptor are
undesirable, such a procedure for the synthesis of
N,N-disubstituted carboxylic acid amides attracts inter-
est from both preparative and analytical viewpoints.
10 ml of benzene, and the mixture was stirred for 3 h
at room temperature. The precipitate of N-ethylaniline
hydroiodide, 2.7 g (91%), was filtered off, and the
solvent was distilled off from the filtrate. Yield 0.54 g,
mp 49–50°C; published data [7]: mp 50°C. Mass spec-
trum, m/z (Irel, %): 163 (15) [M]+ , 148 (3), 135 (10),
106 (75), 77 (15), 51 (10).
b. Acetyl iodide, 4.43 g (26 mmol), was added
dropwise under stirring to 7.78 g (52 mmol) of N,N-di-
ethylaniline, and the mixture was stirred for 3 h at
room temperature. The precipitate of N,N-diethylani-
line hydroiodide was filtered off, and 4.72 g of unre-
acted N,N-diethylaniline (conversion 39%) was dis-
tilled off from the filtrate to isolate the target amide.
Yield 0.38 g (23% on the reacted N,N-diethylaniline),
mp 50–52°C. Mass spectrum, m/z (Irel, %): 162 (5)
[M]+, 149 (35), 134 (90), 106 (65), 77 (40), 51 (25).
EXPERIMENTAL
The H and 13C NMR spectra were recorded on
1
a Bruker DPX-400 spectrometer at 400.13 MHz for 1H
and 100.58 MHz for 13C using CDCl3 as solvent and
tetramethylsilane or cyclohexane as internal reference.
The reaction mixtures were analyzed, and the purity of
products was checked, by GLC on a Tsvet-500 chro-
matograph equipped with a thermal conductivity detec-
tor and a 3-m×4-mm glass column packed with 10%
of PSM-1000 on Inerton-Super (0.125–0.150 mm);
carrier gas helium.
N-Ethyl-N-phenylbenzamide. a. Benzoyl iodide,
2.78 g (12 mmol), was added dropwise under stirring
to a solution of 2.9 g (24 mmol) of N-ethylaniline in
10 ml of benzene, and the mixture was stirred for 8 h
at 78°C. The precipitate of N-ethylaniline hydroiodide
was filtered off, and the solvent was distilled off from
the filtrate. Yield 2.49 g (92%), mp 56–58°C; pub-
Initial acetyl and benzoyl iodides were prepared by
reaction of the corresponding acyl chloride with anhy-
drous sodium iodide [4].
N-Phenylacetamide. Acetyl iodide, 2.04 g
(12 mmol), was added dropwise under stirring to a so-
lution of 2.2 g (24 mmol) of aniline in 10 ml of ben-
zene, and the mixture was stirred for 3 h at room tem-
perature. The precipitate of phenylammonium iodide,
2.09 g (79%), was filtered off, and the product was
isolated by removal of the solvent from the filtrate.
Yield 0.96 g (59%), mp 113–115°C; published data [5]:
1
lished data [7]: mp 58°C. H NMR spectrum, δ, ppm:
1.12 t (3H, CH3), 3.25 q (2H, CH2 ), 6.98–7.87 m
(10H, Ph). 13C NMR spectrum, δC, ppm: 12.49 (CH3),
44.86 (CH2), 127.1–142.9 (Carom), 169.28 (C=O).
b. Benzoyl iodide, 6.62 g (28.5 mmol), was added
dropwise under stirring to 8.51 g (57 mmol) of N,N-di-
ethylaniline, and the mixture was stirred for 21 h at
78°C. Distillation gave 3.1 g of unreacted N,N-diethyl-
aniline (conversion 64%). Yield of N-ethyl-N-phenyl-
benzamide 1.22 g (30%, calculated on the reacted
N,N-diethylaniline), mp 57–59°C. Mass spectrum, m/z
(Irel, %): 225 (10) [M]+ , 207 (5), 197 (3), 147 (2), 132
(2), 120 (3), 105 (75), 77 (55), 51 (22), 36 (18).
1
mp 114°C. H NMR spectrum, δ, ppm: 2.14 s (3H,
CH3), 7.70 m (1H, NH), 7.05–7.48 m (5H, Ph).
13C NMR spectrum, δC, ppm: 24.38 (CH3), 119.9–
138.09 (Ph), 168.17 (C=O). Mass spectrum, m/z
(Irel, %): 135 (20) [M]+, 93 (100), 77 (5), 66 (25), 51
(10), 43 (45).
N-Phenylbenzamide. Benzoyl iodide, 2.8 g
(12 mmol), was added dropwise under stirring to a so-
lution of 2.2 g (24 mmol) of aniline in 10 ml of ben-
zene, and the mixture was stirred for 8 h at 78°C. The
precipitate was filtered off, and the solvent was dis-
tilled off from the filtrate. Yield 0.9 g (39%), mp 160–
N,N-Diethylacetamide. Acetyl iodide, 15.63 g
(92 mmol), was added dropwise under stirring to
28.34 g (280 mmol) of triethylamine, and the mixture
was stirred for 5 h at room temperature. The precipitate
of triethylamine hydroiodide, 6 g (25%), was filtered
off, and the filtrate was subjected to vacuum distilla-
tion to isolate 1.57 g (15%) of N,N-diethylacetamide,
bp 57°C (7 mm), nD20 = 1.4353; published data [8]:
bp 185–186°C, nD20 = 1.4374. Mass spectrum, m/z
(Irel, %): 115 (72) [M]+, 100 (10), 86 (5), 72 (26), 58
(100), 44 (27), 30 (9).
1
164°C; published data [6]: mp 161°C. H NMR spec-
trum, δ, ppm: 8.94 s (1H, NH), 7.10–7.85 m (10H, Ph).
13C NMR spectrum, δC, ppm: 119.6–137.5 (Carom),
164.9 (C=O). Found, %: C 72.07; H 5.73; N 7.40.
C13H11NO. Calculated, %: C 72.21; H 5.60; N 7.10.
N-Ethyl-N-phenylacetamide. a. Acetyl iodide,
2.04 g (12 mmol), was added dropwise under stirring
to a solution of 2.9 g (24 mmol) of N-ethylaniline in
N,N-Diethylbenzamide. Benzoyl iodide, 2.51 g
(11 mmol), was added dropwise under stirring to
2.32 g (23 mmol) of triethylamine, and the mixture
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ACYL IODIDES IN ORGANIC SYNTHESIS: XI.
483
was stirred for 5 h at room temperature. The precipitate
was filtered off, and the filtrate was subjected to
vacuum distillation. Yield 1.15 g (59%), bp 89°C
(1 mm), nD20 = 1.4370; published data [9]: bp 280–
282°C, nD20 = 1.4374. Mass spectrum, m/z (Irel, %): 177
(31) [M]+, 162 (2), 148 (5), 105 (100), 77 (50), 44 (27),
51 (20).
iodide (identified by GLC) and 1.17 g (62%) of
N,N-diallylbenzamide, bp 130°C (1 mm); published
1
data [13]: bp 101°C (0.25 mm). H NMR spectrum, δ,
ppm: 3.82 d (2H, CH2N ), 4.07 d (2H, CH2N), 5.20 m
(4H, CH2=), 5.75 m (2H, CH=), 7.25–7.30 m (5H, Ph).
13C NMR spectrum, δC, ppm: 46.82 and 50.56 (CH2N);
123.81 (CH2=); 136.05 (CH=); 126.39, 128.17, 129.43
(Carom); 171.58 (C=O).
N,N-Dibutylacetamide. Acetyl iodide, 1.7 g
(10 mmol), was added dropwise under stirring to a so-
lution of 1.85 g (10 mmol) of tributylamine in 5 ml of
methylene chloride, and the mixture was stirred for
10 h at 40°C. Distillation gave 0.38 g (21%) of butyl
iodide, bp 130°C, and 0.35 g (16%) of N,N-dibutyl-
acetamide, bp 110°C (8 mm); published data [10]:
Reaction of acetyl iodide with N,N-dimethyl-
phenylmethanamine. Acetyl iodide, 1.7 g (10 mmol),
was added dropwise under stirring to a solution of
1.35 g (10 mmol) of N,N-dimethylphenylmethanamine
in 5 ml of methylene chloride, and the mixture was
stirred for 3.5 h at 40°C. The solvent was distilled off,
and the solid residue was analyzed by GLC and GC–
MS to identify 0.645 g (48%) of unreacted N,N-di-
methylphenylmethanamine {mass spectrum, m/z
(Irel, %): 135 [M]+, 91 (91), 77 (10), 65 (21), 58 (100),
42 (20)}, 0.654 g (30%) of benzyl iodide {mass spec-
trum, m/z (Irel, %): 218 [M]+, 127 (6), 91 (100), 65
(16)}, and 0.104 g (12%) of N,N-dimethylacetamide
{mass spectrum, m/z (Irel, %): 87 [M]+, 72 (25), 44
(96), 43 (44), 15 (5)}.
Reaction of benzoyl iodide with N,N-dimethyl-
phenylmethanamine. Benzoyl iodide, 2.32 g
(10 mmol), was added dropwise under stirring to a so-
lution of 1.35 g (10 mmol) of N,N-dimethylphenyl-
methanamine in 5 ml of methylene chloride, and the
mixture was stirred for 3 h at 40°C. The solvent was
distilled off, and the residue was analyzed by GLC and
GC–MS to identify 0.18 g (13%) of initial N,N-di-
methylphenylmethanamine {mass spectrum, m/z
(Irel, %): 135 [M]+, 91 (100), 77 (10), 58 (100), 42
(20)}, 0.43 g (20%) of benzyl iodide {mass spectrum,
m/z (Irel, %): 218 [M]+, 127 (6), 91 (100), 65 (16)}, and
0.77 g (51.4%) of N,N-dimethylbenzamide {mass
spectrum, m/z (Irel, %): 225 [M]+, 148 (73), 105 (100),
77 (60), 51 (15)}.
1
bp 110–112°C (8 mm). H NMR spectrum, δ, ppm:
0.84–0.89 t (6H, CH3 ), 1.25–1.40 m (4H, CH2), 1.99 s
(3H, MeCO), 2.72–3.46 m (4H, CH2N). 13C NMR
spectrum, δC, ppm: 13.62 (CH3), 20.27 (C2H5), 30.93
(CH2CH2), 45.33 (CH2N), 48.46 (CH2N), 21.39
(MeCO), 169.85 (C=O).
N,N-Dibutylbenzamide. Benzoyl iodide, 2.32 g
(10 mmol), was added dropwise under stirring to a so-
lution of 1.85 g (10 mmol) of tributylamine in 5 ml of
methylene chloride, and the mixture was stirred for
10 h at 40°C. Distillation gave 0.46 g (25%) of butyl
iodide, bp 130°C (identified by GLC), and 1.97 g
(85%) of N,N-dibutylbenzamide, bp 95°C (2 mm);
1
published data [11]: bp 122–125°C (7 mm). H NMR
spectrum, δ, ppm: 0.92–0.94 t (6H, CH3 ); 1.36–1.44 m
(4H, CH2); 3.16–3.46 m (4H, CH2N); 7.27 m, 7.33 m,
7.49 m, 8.12 m (5H, Harom). Mass spectrum, m/z
(Irel, %): 233 (2) [M]+, 218 (2), 204 (5), 190 (3), 176
(5), 160 (2), 105 (60), 77 (85), 41 (100).
N,N-Diallylacetamide. Acetyl iodide, 2.07 g
(12 mmol), was added dropwise under stirring to
1.67 g (12 mmol) of triallylamine, and the mixture was
stirred for 3 h at 40°C. Distillation gave 0.48 g (30%)
1
of allyl iodide, bp 103°C (identified by the H and
The elemental compositions of all isolated products
were consistent with the calculated data.
13C NMR spectra), and 0.52 g (37%) of N,N-diallyl-
acetamide, bp 61°C (2 mm); published data [12]:
1
This study was performed under financial support
by the President of the Russian Federation (program
for support of leading scientific schools, project
no. 4575.2006.3) and by the Integration Project of the
Presidium of the Siberian Division of the Russian
Academy of Sciences (project no. 4.2).
bp 98–100°C (13 mm). H NMR spectrum, δ, ppm:
2.03 s (CH3), 3.81 d (2H, CH2N ), 3.92 d (2H, CH2N),
5.10–5.19 m (4H, CH2=), 5.68–5.85 m (2H, CH=).
13C NMR spectrum, δC, ppm: 20.89 (CH3), 47.30
(CH2N), 49.54 (CH2N), 129.09 (CH2=), 123.85 (CH2=),
170.09 (C=O).
N,N-Diallylbenzamide. Benzoyl iodide, 2.32 g
(10 mmol), was added dropwise under stirring to a so-
lution of 1.37 g (10 mmol) of triallylamine in 5 ml of
methylene chloride, and the mixture was stirred for
3.5 h at 40°C. Distillation gave 0.15 g (10%) of allyl
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